Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium
- Autores
- Donoso, Paulin; Finkelstein, José Pablo; Montecinos, Luis; Said, Matilde; Sánchez, Gina; Vittone, Leticia Beatriz; Bull, Ricardo
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The response of ryanodine receptor (RyR) channels to cytoplasmic free calcium concentration ([Ca2 +]) is redox sensitive. Here, we report the effects of a mild oxidative stress on cardiac RyR (RyR2) channels in Langendorff perfused rat hearts. Single RyR2 channels from control ventricles displayed the same three responses to Ca2 + reported in other mammalian tissues, characterized by low, moderate, or high maximal activation. A single episode of 5 min of global ischemia, followed by 1 min of reperfusion, enhanced 2.3-fold the activity of NOX2 compared to controls and changed the frequency distribution of the different responses of RyR2 channels to calcium, favoring the more active ones: high activity response increased and low activity response decreased with respect to controls. This change was fully prevented by perfusion with apocynin or VAS 2870 before ischemia and totally reversed by the extension of the reperfusion period to 15 min. In vitro activation of NOX2 in control SR vesicles mimicked the effect of the ischemia/reperfusion episode on the frequencies of emergence of single RyR2 channel responses to [Ca2 +] and increased 2.2-fold the rate of calcium release in Ca2 +-loaded SR vesicles. In vitro changes were reversed at the single channel level by DTT and in isolated SR vesicles by glutaredoxin. Our results indicate that in whole hearts a mild oxidative stress enhances the response of cardiac RyR2 channels to calcium via NOX2 activation, probably by S-glutathionylation of RyR2 protein. This change is transitory and fully reversible, suggesting a possible role of redox modification in the physiological response of cardiac RyR2 to cellular calcium influx.
Fil: Donoso, Paulin. Universidad de Chile; Chile
Fil: Finkelstein, José Pablo. Universidad de Chile; Chile
Fil: Montecinos, Luis. Universidad de Chile; Chile
Fil: Said, Matilde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Sánchez, Gina. Universidad de Chile; Chile
Fil: Vittone, Leticia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Bull, Ricardo. Universidad de Chile; Chile - Materia
-
Ca2 +-Induced Ca2 + Release
Redox Signaling
Single Channel
Preconditioning
Ischemia/Reperfusion - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/11952
Ver los metadatos del registro completo
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Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calciumDonoso, PaulinFinkelstein, José PabloMontecinos, LuisSaid, MatildeSánchez, GinaVittone, Leticia BeatrizBull, RicardoCa2 +-Induced Ca2 + ReleaseRedox SignalingSingle ChannelPreconditioningIschemia/Reperfusionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The response of ryanodine receptor (RyR) channels to cytoplasmic free calcium concentration ([Ca2 +]) is redox sensitive. Here, we report the effects of a mild oxidative stress on cardiac RyR (RyR2) channels in Langendorff perfused rat hearts. Single RyR2 channels from control ventricles displayed the same three responses to Ca2 + reported in other mammalian tissues, characterized by low, moderate, or high maximal activation. A single episode of 5 min of global ischemia, followed by 1 min of reperfusion, enhanced 2.3-fold the activity of NOX2 compared to controls and changed the frequency distribution of the different responses of RyR2 channels to calcium, favoring the more active ones: high activity response increased and low activity response decreased with respect to controls. This change was fully prevented by perfusion with apocynin or VAS 2870 before ischemia and totally reversed by the extension of the reperfusion period to 15 min. In vitro activation of NOX2 in control SR vesicles mimicked the effect of the ischemia/reperfusion episode on the frequencies of emergence of single RyR2 channel responses to [Ca2 +] and increased 2.2-fold the rate of calcium release in Ca2 +-loaded SR vesicles. In vitro changes were reversed at the single channel level by DTT and in isolated SR vesicles by glutaredoxin. Our results indicate that in whole hearts a mild oxidative stress enhances the response of cardiac RyR2 channels to calcium via NOX2 activation, probably by S-glutathionylation of RyR2 protein. This change is transitory and fully reversible, suggesting a possible role of redox modification in the physiological response of cardiac RyR2 to cellular calcium influx.Fil: Donoso, Paulin. Universidad de Chile; ChileFil: Finkelstein, José Pablo. Universidad de Chile; ChileFil: Montecinos, Luis. Universidad de Chile; ChileFil: Said, Matilde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Sánchez, Gina. Universidad de Chile; ChileFil: Vittone, Leticia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Bull, Ricardo. Universidad de Chile; ChileElsevier2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/11952Donoso, Paulin; Finkelstein, José Pablo; Montecinos, Luis; Said, Matilde; Sánchez, Gina; et al.; Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium; Elsevier; Journal Of Molecular And Cellular Cardiology; 68; 3-2014; 38–460022-2828enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.yjmcc.2013.12.028info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022282814000066info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:10Zoai:ri.conicet.gov.ar:11336/11952instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:59:11.16CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium |
| title |
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium |
| spellingShingle |
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium Donoso, Paulin Ca2 +-Induced Ca2 + Release Redox Signaling Single Channel Preconditioning Ischemia/Reperfusion |
| title_short |
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium |
| title_full |
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium |
| title_fullStr |
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium |
| title_full_unstemmed |
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium |
| title_sort |
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium |
| dc.creator.none.fl_str_mv |
Donoso, Paulin Finkelstein, José Pablo Montecinos, Luis Said, Matilde Sánchez, Gina Vittone, Leticia Beatriz Bull, Ricardo |
| author |
Donoso, Paulin |
| author_facet |
Donoso, Paulin Finkelstein, José Pablo Montecinos, Luis Said, Matilde Sánchez, Gina Vittone, Leticia Beatriz Bull, Ricardo |
| author_role |
author |
| author2 |
Finkelstein, José Pablo Montecinos, Luis Said, Matilde Sánchez, Gina Vittone, Leticia Beatriz Bull, Ricardo |
| author2_role |
author author author author author author |
| dc.subject.none.fl_str_mv |
Ca2 +-Induced Ca2 + Release Redox Signaling Single Channel Preconditioning Ischemia/Reperfusion |
| topic |
Ca2 +-Induced Ca2 + Release Redox Signaling Single Channel Preconditioning Ischemia/Reperfusion |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
The response of ryanodine receptor (RyR) channels to cytoplasmic free calcium concentration ([Ca2 +]) is redox sensitive. Here, we report the effects of a mild oxidative stress on cardiac RyR (RyR2) channels in Langendorff perfused rat hearts. Single RyR2 channels from control ventricles displayed the same three responses to Ca2 + reported in other mammalian tissues, characterized by low, moderate, or high maximal activation. A single episode of 5 min of global ischemia, followed by 1 min of reperfusion, enhanced 2.3-fold the activity of NOX2 compared to controls and changed the frequency distribution of the different responses of RyR2 channels to calcium, favoring the more active ones: high activity response increased and low activity response decreased with respect to controls. This change was fully prevented by perfusion with apocynin or VAS 2870 before ischemia and totally reversed by the extension of the reperfusion period to 15 min. In vitro activation of NOX2 in control SR vesicles mimicked the effect of the ischemia/reperfusion episode on the frequencies of emergence of single RyR2 channel responses to [Ca2 +] and increased 2.2-fold the rate of calcium release in Ca2 +-loaded SR vesicles. In vitro changes were reversed at the single channel level by DTT and in isolated SR vesicles by glutaredoxin. Our results indicate that in whole hearts a mild oxidative stress enhances the response of cardiac RyR2 channels to calcium via NOX2 activation, probably by S-glutathionylation of RyR2 protein. This change is transitory and fully reversible, suggesting a possible role of redox modification in the physiological response of cardiac RyR2 to cellular calcium influx. Fil: Donoso, Paulin. Universidad de Chile; Chile Fil: Finkelstein, José Pablo. Universidad de Chile; Chile Fil: Montecinos, Luis. Universidad de Chile; Chile Fil: Said, Matilde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina Fil: Sánchez, Gina. Universidad de Chile; Chile Fil: Vittone, Leticia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina Fil: Bull, Ricardo. Universidad de Chile; Chile |
| description |
The response of ryanodine receptor (RyR) channels to cytoplasmic free calcium concentration ([Ca2 +]) is redox sensitive. Here, we report the effects of a mild oxidative stress on cardiac RyR (RyR2) channels in Langendorff perfused rat hearts. Single RyR2 channels from control ventricles displayed the same three responses to Ca2 + reported in other mammalian tissues, characterized by low, moderate, or high maximal activation. A single episode of 5 min of global ischemia, followed by 1 min of reperfusion, enhanced 2.3-fold the activity of NOX2 compared to controls and changed the frequency distribution of the different responses of RyR2 channels to calcium, favoring the more active ones: high activity response increased and low activity response decreased with respect to controls. This change was fully prevented by perfusion with apocynin or VAS 2870 before ischemia and totally reversed by the extension of the reperfusion period to 15 min. In vitro activation of NOX2 in control SR vesicles mimicked the effect of the ischemia/reperfusion episode on the frequencies of emergence of single RyR2 channel responses to [Ca2 +] and increased 2.2-fold the rate of calcium release in Ca2 +-loaded SR vesicles. In vitro changes were reversed at the single channel level by DTT and in isolated SR vesicles by glutaredoxin. Our results indicate that in whole hearts a mild oxidative stress enhances the response of cardiac RyR2 channels to calcium via NOX2 activation, probably by S-glutathionylation of RyR2 protein. This change is transitory and fully reversible, suggesting a possible role of redox modification in the physiological response of cardiac RyR2 to cellular calcium influx. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014-03 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/11952 Donoso, Paulin; Finkelstein, José Pablo; Montecinos, Luis; Said, Matilde; Sánchez, Gina; et al.; Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium; Elsevier; Journal Of Molecular And Cellular Cardiology; 68; 3-2014; 38–46 0022-2828 |
| url |
http://hdl.handle.net/11336/11952 |
| identifier_str_mv |
Donoso, Paulin; Finkelstein, José Pablo; Montecinos, Luis; Said, Matilde; Sánchez, Gina; et al.; Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium; Elsevier; Journal Of Molecular And Cellular Cardiology; 68; 3-2014; 38–46 0022-2828 |
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eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yjmcc.2013.12.028 info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022282814000066 |
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